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- Creators: Chemical Engineering Program
- Creators: Ankeny, Casey
- Creators: Blain Christen, Jennifer
Description
The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.
ContributorsFauer, Chase Alexander (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still have some way to go before they are viable systems for drug delivery. One of the main reasons for this is a lack of fabrication processes and systems which produce monodisperse particles while also being feasible for industrialization [10]. This honors thesis investigates various microparticle fabrication techniques \u2014 two using mechanical agitation and one using fluid dynamics \u2014 with the long term goal of incorporating norepinephrine and adenosine into the particles for metabolic stimulatory purposes. It was found that mechanical agitation processes lead to large values for dispersity and the polydispersity index while fluid dynamics methods have the potential to create more uniform and predictable outcomes. The research concludes by needing further investigation into methods and prototype systems involving fluid dynamics methods; however, these systems yield promising results for fabricating monodisperse particles which have the potential to encapsulate a wide variety of therapeutic drugs.
ContributorsRiley, Levi Louis (Author) / Vernon, Brent (Thesis director) / VanAuker, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Imaging analysis of local drug delivery is important because in both studies involving chemotherapy targeted toward glioblastoma and antimicrobial addressing infection, the drug concentration and distribution are unknown. There are a variety of studies focused on the local delivery of drug to a targeted location, but we are presenting a way of quantifying the concentration of the drug and the distribution of the drug during a period of time. This study aims to do that by utilizing Materialise Mimics to analyze the MRI images of local drug delivery in glioblastoma in canines and antimicrobial gel in rabbit femurs. The focus of the technique is to register the anatomy in T1-weighted spin echo images to the drug delivery in T2 flow attenuated inversion recovery (FLAIR) images in order to see where the drug went and did not go relative to the anatomical part. Both studies focus on addressing effective volumes of drug to a designated anatomical area, in which the delivery can be difficult as it involves bypassing the blood brain barrier in the first study and achieving effective volumes while preventing toxicity to the kidneys in the second study. The goal of this project lies in determining the drug volumes and location for the specified duration and anatomical part.
ContributorsJehng, Hope (Author) / Caplan, Michael (Thesis director) / Sirianni, Rachael (Committee member) / Chemical Engineering Program (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The objective of this research is to create biodegradable mats with tunable characteristics such as fiber diameter and surface area. The drug delivery mats enable spatially controlled delivery of disease-specific therapeutics. Using a large electric potential to draw fibers from a solution flowing at a specific rate, the polymer fibers reach a grounded target several inches away. The biodegradable polymer used in this study was poly(lactic acid-co-glycolic acid) (PLGA). PLGA solutions ranging from 0.5 to 27 wt.% were prepared by dissolving the block copolymer in a solvent mixture containing tetrahydrofuran (THF) and dimethylformamide (DMF) at a 3:1 weight ratio. They were then electrospun at needle-to-target distances of 7, 14, and 18 cm and rates ranging from 0.8 to 4 mL/h. The range of voltage used was between 8 – 15 kV, which was based on the observation of the formation of a Taylor cone, largely affected by on the environment and weather (e.g., temperature and humidity in the lab). A 27 wt.% PLGA solution, electrospun at 1 mL/h at a voltage of 11.25 kV and needle-to-target distance of 14 cm produced uniform fibers with an average fiber diameter of 0.985 m. All other parameters outside the range given created beaded fibers. In addition, solution rheology was performed on some of the PLGA solution to measure viscosity, which is directly correlated to the fiber diameter of the electrospun mats. Observing the impact of solvent on fiber spinning and fiber diameter brings about many positive results in developing fully characterized and well-understood fibrous mats for drug delivery. The nanoscale fibers will be used as drug delivery mats and, therefore, the biodegradation kinetics of the polymers will be studied. Next, parameters of the polymers as well as the polymeric mats will be correlated to the degradation-mediated release of small molecule therapeutics (e.g., peptides, drugs, etc.) such that time-resolved dosing profiles can be created.
ContributorsLent, Madeline (Author) / Green, Matthew (Thesis director) / Holloway, Julianne (Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo from the bodily environment, and reduction in systemic side effects. This experiment used a single emulsion technique to encapsulate L-tyrosine in PLGA microparticles and UV spectrophotometry to analyze the drug release over a period of one week. The release assay found that for the tested samples, the released amount is distinct initially, but is about the same after 4 days, and they generally follow the same normalized percent released pattern. The experiment could continue with testing more samples, test the same samples for a longer duration, and look into higher w/w concentrations such as 20% or 50%.
ContributorsSeo, Jinpyo (Author) / Vernon, Brent (Thesis director) / Pal, Amrita (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Cellular assays are the backbone of biological studies - be it for tissue modeling, drug discovery, therapeutics, or diagnostics. Two-dimensional (2D) cell culture has been deployed for several decades to garner physiologically relevant information and predict data before the cost-intensive animal testing. Although 2D techniques have been valuable for cellular assays, they have a colossal limitation - they do not adequately consider the natural three-dimensional (3D) microenvironment of the cells. As a result, they sometimes provide misleading statistics. Therefore, it is important to develop a 3D model that predicts cellular behaviors and their interaction with neighboring cells and extracellular matrix (ECM) in a more realistic manner. In recent biomedical research, various platforms have been modeled to generate 3D prototypes of tissues, spheroids, in vitro that could allow the study of cellular responses resembling in vivo environments, such as matrices, scaffolds, and devices. But most of these platforms have drawbacks such as lack of spheroid size control, low yield, or high cost associated with them. On the other hand, Amikagel is a low cost, high-fidelity platform that can facilitate the convenient generation of tumor and stem cell spheroids. Furthermore, Amikabeads are aminoglycoside-derived hydrogel microbeads derived from the same monomers as Amikagel. They are a versatile platform with several chemical groups that can be exploited for encapsulating the spheroids and investigating the delivery of bioactive compounds to the cells. This thesis is focused on engineering novel 3D tumor and stem cell models generated on Amikagel and encapsulated in Amikabeads for proximal delivery of bioactive compounds and applications in regenerative medicine.
ContributorsNanda, Tanya (Author) / Rege, Kaushal (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Weaver, Jessica (Committee member) / Arizona State University (Publisher)
Created2020